Various implantable medical devices are advantageously inserted within various body vessels to treat various conditions. Minimally invasive techniques and instruments for placement of intraluminal medical devices, such as stent grafts, have been developed to treat and repair undesirable conditions within body vessels, including treatment of conditions that affect fluid flow within a body vessel.
Biliary tract cancers, also called cholangiocarcinomas, refer to malignancies occurring in the organs of the biliary system, including pancreatic cancer, gallbladder cancer, and cancer of bile ducts. In the United States, an estimated 20,000 new cases of liver and biliary tract cancer are diagnosed annually. Biliary tract cancer is the second most common primary hepatobiliary cancer, after hepatocellular cancer. Approximately 7,500 new cases of biliary tract cancer are diagnosed each year; about 5,000 of these are gallbladder cancer, and between 2,000 and 3,000 are bile duct cancers.
Tumor growth may obstruct the body vessels, such as biliary ducts. For example, the biliary system, which drains bile from the liver into the duodenum, may be obstructed by (1) a tumor composed of bile duct cells (cholangiocarcinoma), (2) a tumor which invades the bile duct (e.g., pancreatic carcinoma), or (3) a tumor which exerts extrinsic pressure and compresses the bile duct (e.g., enlarged lymph nodes). One example of primary biliary tumors are adenocarcinoma (which are also called Klatskin tumors when found at the bifurcation of the common hepatic duct). These tumors are also referred to as biliary carcinomas, choledocholangio-carcinomas, or adenocarcinomas of the biliary system. Benign tumors which affect the bile duct (e.g., adenoma of the biliary system), and, in rare cases, squamous cell carcinomas of the bile duct and adenocarcinomas of the gallbladder, may also cause compression of the biliary tree and therefore, result in biliary obstruction. Tumor overgrowth of the common bile duct results in progressive cholestatic jaundice.
Most of the tumors from the pancreas arise from cells of the pancreatic ducts. This is a highly fatal form of cancer (5% of all cancer deaths; 26,000 new cases per year in the U.S.) with an average of 6 months survival and a 1 year survival rate of only 10%. When these tumors are located in the head of the pancreas they frequently cause biliary obstruction, and this detracts significantly from the quality of life of the patient. While all types of pancreatic tumors are generally referred to as “carcinoma of the pancreas” there are histologic subtypes including: adenocarcinoma, adenosquamous carcinoma, cystadeno-carcinoma, and acinar cell carcinoma. Hepatic tumors, may also cause compression of the biliary tree, and therefore cause obstruction of the biliary ducts.
Implantable medical devices may be used to maintain body vessel patency while delivering a therapeutic agent proximate the site of implantation. For example, stent grafts may be configured for insertion in a biliary or pancreatic body vessel. Intraluminal medical devices can be deployed in a body vessel at a point of treatment and the delivery device subsequently withdrawn from the vessel, while the medical device is retained within the vessel to provide sustained improvement in vascular valve function or to increase vessel patency.
Both primary biliary tumors, as well as other tumors which cause compression of the biliary tree, may be treated by implanting a stent graft configured to release a therapeutic agent. The stent graft may further comprise a releasable therapeutic agent within the body vessel to treat a disease condition, such as a localized tumor, proximate an implantation site. A releasable therapeutic agent may be combined with a stent graft, or other implantable medical devices, in various ways, including: (a) by directly affixing the therapeutic agent to the implant or device (e.g., by either spraying the implant or device with a polymer/drug film, or by dipping the implant or device into a polymer/drug solution, or by other covalent or noncovalent means); (b) by coating the implant or device with a substance such as a hydrogel which will in turn absorb the therapeutic agent; (c) by interweaving a therapeutic agent-coated thread (or the polymer itself formed into a thread) into the medical device; (d) by inserting the medical device into a sleeve or mesh which comprises or is coated with the therapeutic agent; (e) constructing the medical device itself with the therapeutic agent; or (f) by otherwise adapting the medical device to release the therapeutic agent. For example, published U.S. patent application no. US2005/0220835 A1 by Jayaraman et al., filed Mar. 30, 2004, discloses implantable medical devices comprising a polyetherurethane modified by admixture with a siloxane surface modifying additive in combination with a releasable therapeutic agent.
One or more intraluminal medical devices can be introduced to a point of treatment within a body vessel using a delivery catheter device passed through the vasculature communicating between a remote introductory location and the implantation site, and released from the delivery catheter device at the point of treatment within the body vessel. Radially expandable stent grafts comprising a releasable therapeutic agent in the graft material are typically radially compressed to a low-profile configuration and inserted into a delivery catheter system. The stent grafts may be configured for expansion within a body vessel by balloon expansion or self-expansion. Once expanded, the stent grafts may resist radial compression. Failure of the graft material to radially compress to a desired radial profile may result in undesirable levels of friction on the graft material when loading the stent graft into the delivery catheter. Undesirable levels of friction on the stent graft may compromise the mechanical integrity of the graft or reduce retention of the therapeutic agent within the device, compromising the therapeutic effectiveness of the device.
What is needed are implantable stent grafts comprising a therapeutically effective amount of a releasable therapeutic agent that are configured to withstand radial compression without undesirably compromising the integrity of the stent graft or loading of the therapeutic agent. Also needed are stent grafts providing a desirably sustained release of the therapeutic agent.